Endurance training mitigates morphine-induced renal dysfunction in young and aged rats: involvement of oxidative stress, SIRT1, Klotho and TFAM.

<h4>Background</h4>Chronic morphine consumption induces oxidative stress and renal dysfunction, effects that may be exacerbated by aging-related declines in adaptive capacity. Regular endurance exercise enhances antioxidant defense and mitochondrial regulation; however, its ability to counteract morphine-induced renal alterations across different stages of aging remains insufficiently characterized.<h4>Methods</h4>Male wistar rats, categorized as young and aged based on chronological age and body weight, were allocated to control, morphine, exercise, and morphine plus exercise groups within each age category. Morphine was administered via drinking water for four weeks. Concurrently, animals in the exercise groups performed moderate-intensity continuous training on a treadmill. At study completion, serum and renal tissues were collected for assessment of oxidative stress markers (MDA, TAC, SOD), MPO, renal function indices (BUN and creatinine), and renal expression of sirtuin 1 (SIRT1) and Klotho, Mitochondrial compatibility markers (Citrate synthase activity and TFAM).<h4>Results</h4>Chronic morphine exposure was associated with increased oxidative stress markers and decreased antioxidant capacity in kidney tissue, and simultaneously increased serum urea and creatinine levels in young and old mice, indicating impaired renal functional status. Chronic morphine administration also decreased SIRT1 and Klotho levels in young and old animals. In contrast, 4 weeks of endurance training improved markers of mitochondrial adaptation, oxidative balance, and renal function, which were associated with increased expression of SIRT1 and Klotho in kidney tissue. These changes could indicate a potential link between exercise training and molecular pathways involved in the regulation of oxidative stress and renal homeostasis. However, these findings suggest an association, and causal or mechanistic interpretations will require further investigation in future studies.<h4>Conclusion</h4>These findings indicate that endurance training is associated with more favorable renal biomarker profiles in the context of chronic opioid exposure.